The mechanisms of cadmium carcinogenesis are under active investigation at the organismal, cellular and molecular levels. On the organismal level, cadmium injected subcutaneously in rats was found to induce tumors at the site of injection in an apparent dose-related fashion while cadmium-induced testicular tumors appeared to involve a threshold phenomenon. A possible association between cadmium treatment and prostatic tumors was also seen. Acutely, cadmium induced extensive necrotic lesions in the ovaries of hamsters, similar to what is seen in the testes. A series of experiments on the cellular level indicated that tolerance to cadmium was highly dependent on genetic capacity for the production of the metal-binding protein, metallothionein. Pharmacologic manipulations that resulted in hypomethylation of DNA also resulted in increased capacity for metallothionein synthesis and induction of tolerance to cadmium cytotoxicity in cell culture. On the molecular level, investigations into the nature of the metal-binding proteins of the rat testes showed that in this target tissue of cadmium carcinogenesis there is a clear absence of metallothionein, indicating that the capacity for the production of this protein may be an important determinant in the target site specificity of cadmium.